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  • 1
    Electronic Resource
    Electronic Resource
    Central action of benserazide after COMT inhibition demonstrated in vivo by PET (1991)
    Springer
    Journal of neural transmission 85 (1991), S. 11-17 
    Details
    ISSN: 1435-1463
    Keywords: Tomography ; monkey ; L-DOPA ; aromatic L-amino acid decarboxylase ; catechol-O-methyltransferase ; Parkinson's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Positron emission tomography (PET) following intravenous administration of β-[11 C]-L-DOPA provides a method of assessing regional cerebral uptake and utilization of levodopa. Cerebral levodopa kinetics in the rhesus monkey were investigated after the inhibition of catechol-O-methyltransferase (COMT) with RO 40-7592, and after coadministration of the peripheral aromatic L-amino acid decarboxylase (AADC) inhibitors benserazide and carbidopa. Pretreatment with RO 40-7592 (10 mg/kg), benserazide (10 mg/kg) or carbidopa (3.5 mg/kg) did not change striatal k3, which mainly reflects the ability for the brain tissue to convert [11C]-L-DOPA to [11C]-dopamine, although the brain's uptake of radioactivity increased substantially after pretreatment with the AADC inhibitors. When benserazide was coadministered with RO 40-7592 (10 mg/kg) a dose-dependent decrease in striatal k3 was measured with an apparent ED50 of 3 mg/kg. No such effect was indicated after pretreatment with the combination of RO 40-7592 (10 mg/kg) and carbidopa (3.5 mg/kg). The possible negative interactions of coadministration with COMT inhibitors and predominantly peripherally acting AADC inhibitors must be considered when used in the therapy of Parkinson's disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01244653
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  • 2
    Electronic Resource
    Electronic Resource
    Decreased uptake and binding of11C-nicotine in brain of Alzheimer patients as visualized by positron emission tomography (1990)
    Springer
    Journal of neural transmission 2 (1990), S. 215-224 
    Details
    ISSN: 1435-1463
    Keywords: Positron emission tomography ; PET ; Alzheimer's disease ; (+) (R) N-11C-methyl nicotine ; (−) (S) N-11C-methyl nicotine ; brain ; nicotinic receptors ; cholinergic receptors ; diagnostic marker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Positron emission tomography of the brain following intravenous injection of (+) (R) and (−) (S) N-[11C-methyl]nicotine showed a marked reduced uptake of both isomers, especially the (R) form, in Alzheimer patients as compared to age-matched controls. The significantly larger difference between the uptake values of the (S)- and (R)-enantiomers of11C-nicotine in Azheimer brains may be of diagnostic value.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02257652
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  • 3
    Electronic Resource
    Electronic Resource
    Localization of monoamine oxidase B in human brain by autoradiographical use of11C-labelled L-deprenyl (1989)
    Springer
    Journal of neural transmission 77 (1989), S. 55-64 
    Details
    ISSN: 1435-1463
    Keywords: Cryosection ; autoradiography ; monoamine oxidase ; brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 11C-labelled L-deprenyl in vitro autoradiography was used to study the regional distribution of MAO-B in human brain. 80 μm thick cryosections from two human brains, a 67 years old female and a 58 years old male, were taken on tape/paper and transferred on to a gelatinized glass plate. The sections were then incubated with 34 and 54 nM11C-L-deprenyl for 15 min and exposed to a film sensitive to high energy radiation for 2 hours. The autoradiograms obtained were analyzed by computerized densiotometry. High11C-deprenyl binding was found in the caudate nucleus, putamen, thalamus, substantia nigra, medial and lateral geniculate bodies, hippocampus and periaqueductal gray. Moderate to low binding was observed in cerebral cortex. Cerebral cortex and white matter showed the lowest binding. The autoradiographic technique described proved to be a fast and reliable method to investigate the topographic localization of MAO-B in large cryosections of human brain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01255819
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  • 4
    Electronic Resource
    Electronic Resource
    Regional brain kinetics of 6-fluoro-(β-11C)-L-dopa and (β-11C)-L-dopa following COMT inhibition. A study in vivo using positron emission tomography (1992)
    Springer
    Journal of neural transmission 87 (1992), S. 15-22 
    Details
    ISSN: 1435-1463
    Keywords: (β-11C)-L-dopa ; 6-fluoro-(β-11C)-L-dopa ; positron emission tomography ; catechol-O-methyl transferase ; monkeys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The regional brain kinetics of (β-11C)-L-dopa and 6-fluoro-(β-11C)-L-dopa was measured in six Rhesus monkeys using positron emission tomography (PET). Radioactivity accumulated specifically in the striatal region and the increase in L-dopa-derived radioactivity utilization with time was calculated using surrounding brain as a reference area, this being devoid of dopaminergic activity. The rate constant for selective striatal utilization i.e. grossly decarboxylation was 0.0110 ± 0.0007 (S.D) and 0.0057 ± 0.0006 min1 for (β-11C)-L-dopa and 6-fluoro-(β-11C)-L-dopa, respectively. After pre-treatment of the monkeys with the peripherally and centrally active catecholamine-O-methyl transferase (COMT) inhibitor Ro 40-7592 10 mg/kg, the decarboxylation rate remained unchanged (0.0112 ± 0.0015 min-1) for (β11C)-L-dopa, whereas an increase in rate was measured for 6-fluoro-(β-11C)L-dopa (0.0092 ± 0.0015 min−1). Differences in the distribution of radiolabelled metabolites i.e. the corresponding O-methyl-L-dopa in the reference area is most probably the reason for the difference in calculated decarboxylation rate seen between the radiotracers. The higher decarboxylation rate measured for 6-fluoro-(β-11C)-L-dopa after blockade of COMT shows that the radiolabelled metabolites i.e. 6-fluoro-O-methyl-(β-11C)-L-dopa significantly contributes to background radioactivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01253107
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  • 5
    Electronic Resource
    Electronic Resource
    Uptake and regional distribution of (+)-(R)- and (−)-(S)-N-[methyl-11C]-nicotine in the brains of Rhesus monkey an attempt to study nicotinic receptors in vivo (1989)
    Springer
    Journal of neural transmission 1 (1989), S. 195-205 
    Details
    ISSN: 1435-1463
    Keywords: Monkey ; positron emission tomography ; 11C-nicotine ; optic enantiomers ; nicotinic receptors ; brain ; regional distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary N-[methyl-11C] nicotine (11C-nicotine) was given intravenously to monkeys and the uptake and regional distribution of radioactivity was followed in the brain using positron emission tomography (PET). The11C-radioactivity in the brain peaked within 1–2 min and then rapidly declined. Pretreatment with unlabelled nicotine (10 μg/kg) reduced the uptake of11C-radioactivity to the brain by 30%. The uptake of radioactivity was higher following (+)11C-nicotine than (−)11C-nicotine. Both enantiomers were distributed in a similar manner within the brain. When animals were infused with a peripheral nicotinic blocker (trimetaphan) the uptake of radioactivity to the brain was lower following (+)11C-nicotine compared to (−)11C-nicotine. The amount of radioactivity was high in the occipital cortex, thalamus, intermediate in the frontal cortex and low in white matter in (−)11C injected monkeys while no regional difference in distribution of11C-radioactivity was observed after injection of (+)11C-nicotine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02248669
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  • 6
    Electronic Resource
    Electronic Resource
    Amphetamine effects on dopamine release and synthesis rate studied in the Rhesus monkey brain by positron emission tomography (1997)
    Springer
    Journal of neural transmission 104 (1997), S. 329-339 
    Details
    ISSN: 1435-1463
    Keywords: Amphetamine ; [11C] ; L-DOPA ; raclopride ; N-methylspiperone ; CBF ; PET ; monkeys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Positron emission tomography (PET) was used in a multitracer protocol to evaluate D-amphetamine induced effects on dopamine biosynthesis rate and release in propofol anesthetized Rhesus monkeys.l-[β-11C]DOPA was used as biochemical probe to study the brain dopamine biosynthesis rate whilst dopamine release was followed by the binding displacement of the [11C]-radiolabelled dopamine receptor antagonists, raclopride and N-methylspiperone. Studies were performed with either a constant rate intravenous infusion of D-amphetamine aiming at plasma concentrations of 0.2 to 25 ng/ml or with intravenous bolus doses of 0.1 and 0.4 mg/ kg. Decreased binding of the dopamine receptor antagonists was measured in both modes of D-amphetamine administration but notably [11C]N-methylspiperone was less able to sense D-amphetamine induced release of dopamine. At plasma concentrations aimed above 1 ng/ml a levelling off of the binding of [11C]raclopride at 68 ± 8.1% of the baseline value indicated that displacement was only possible from a fraction of the binding sites. Amphetamine was observed to increase the rate constant forl-[β-11C]DOPA utilization in the brain. This was most likely due to an acutely induced subsensitivity of presynaptic dopamine receptors.l-[β-11C]DOPA and [11C]raclopride were found suitable to indicate changes in dopamine synthesis rate and release respectively using PET and can be used to mirror drug-induced changes of brain dopaminergic function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01277655
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  • 7
    Electronic Resource
    Electronic Resource
    Positron emission tomographic studies on aromatic L-amino acid decarboxylase activity in vivo for L-dopa and 5-hydroxy-L-tryptophan in the monkey brain (1993)
    Springer
    Journal of neural transmission 94 (1993), S. 127-135 
    Details
    ISSN: 1435-1463
    Keywords: 5-Hydroxy-L-(β-11 C)tryptophan ; L-(β-11 C)DOPA ; positron emission tomography ; aromatic amino acid decarboxylase ; monkeys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The regional brain kinetics following 5-hydroxy-L-(β-11 C)tryptophan and L-(β-11 C)DOPA intravenous injection was measured in twelve Rhesus monkeys using positron emission tomography (PET). The radiolabelled compounds were also injected together with various doses of unlabelled 5-hydroxy-L-tryptophan or L-DOPA. The radioactivity accumulated in the striatal region and the rate of increased utilization with time was calculated using a graphical method with back of the brain as a reference region. The rate constants for decarboxylation were 0.0070 ± 0.0007 (S. D) and 0.0121±0.0010min−1 for 5-hydroxy-L-(β-11C)tryptophan and L-(β-11 C)DOPA, respectively. After concomitant injection with unlabelled 5-hydroxy-L-tryptophan, the rate constant of 5-hydroxy-L-(β-11 C)tryptophan decreased dose-dependently and a 50 percent reduction was seen with a dose of about 4mg/kg of unlabelled compound. A decreased utilization rate of L-(β-11 C)DOPA was seen only after simultaneous injection of 30 mg/kg of either L-DOPA or 5-hydroxy-L-tryptophan. This capacity limitation was most likely interpreted as different affinity of the striatal aromatic amino acid decarboxylase for L-DOPA and 5-hydroxy-L-tryptophan, respectively.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01245006
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